Lung cancer is the most common form of cancer in the world, which is estimated to account for 12.3% of all cancers and 17.8% of cancer-related deaths (Parkin, D. M., Lancet Oncol 2001, 2, 533-43). Also, the incidence of lung cancer and the resulting mortality rate in Korea are estimated to continue to increase. Despite the recent development of cancer therapy, the survival rate of lung cancer patients is very low. This is because the cancer is diagnosed at a late stage in most cases. Thus, there is an urgent need to develop markers which can diagnose lung cancer at an early state to increase the survival rate of lung cancer patients.
Meanwhile, human body fluids, such as blood and urine, are useful for recognizing the pathological conditions (conditions associated with tumors, immune responses and vascular diseases) of the body, because they can be easily collected for diagnosis and include secretory proteins which are expressed differently in abnormal and normal conditions. In addition, due to abundant serum proteins (such as albumin, IgG and transferrin), it is difficult to detect low abundant proteins which can be used as new biomarkers. A number of studies have attempted various approaches to reduce abundant serum proteins. Methods for removing the abundant serum proteins were introduced by some researchers and are generally classified into two categories. One of them is the use of an immunoaffinity HPLC column to reduce albumin, IgA, IgG, transferin, haptoglobin (HP) and antitrypsin (Okano, T. et al., Proteomics 2006, 6, 3938-48; Yu, K. H. et al., J Proteome Res 2005, 4, 1742-51). Another is the isolation of serum glycoproteins using hydrazide chemistry (Liu, T. et al., J Proteome Res 2005, 4, 2070-80) or lectin affinity (Yang, Z. et al., J Chromatogr A 2004, 1053, 79-88; Yang, Z. et al., Proteomics 2005, 5, 3353-66; Vosseller, K. et al., Mol Cell Proteomics 2006, 5, 923-34; Zhang, H. et al., Mol Cell Proteomics 2005, 4, 144-55).
Two recent studies reported proteins expressed differently between healthy person's serum and lung cancer patient's serum using 2-DE and MALDI-TOF (Maciel, C. et al., J Exp Ther Oncol 2005, 5, 31-8) or 2-DE and LC-MS/MS (Okano, T. et al., Proteomics 2006, 6, 3938-48), and NSE, CEA and CYFRA 21-1 are currently known as serum markers for lung cancer. However, the sensitivity and specificity thereof as lung cancer markers are not sufficient (Tarro, G. et al., J Cell Physiol 2005, 203, 1-5). For this reason, the development of novel biomarkers specific for lung cancer is urgently needed.